1. Field Of The Invention
This invention relates to a process for decolorizing the colored impurities which occur during the preparation of an N-acetyl aminophenol.
In the past, acylated aminophenols have been used as non-volatile antioxidants for petroleum products, greases, synthetic lubricants and the like. Of this class of acetylated aminophenols, the lower molecular weight members, particularly the N-acetyl alkyl-substituted aminophenols containing lower alkyl nuclear substituents, i.e., having from 1 to 4 carbon atoms, and especially N-acetyl-p-aminophenol, have found extensive use in the pharmaceutical industry as analgesics.
It is well known that aminophenols, and especially ortho- and para-aminophenols, oxidize readily to afford quinone, quinonimine and meriquinonimine color body impurities which impart discoloration to the aminophenol. These impurities are present in crude N-acetyl aminophenol products prepared by reacting aminophenol with an acetylating agent such as acetic anhydride, mixtures of acetic anhydride in acetic acid, acetic acid and the like. When the crude N-acetyl aminophenol is to be used for medicinal purposes or as intermediates in the preparation of other compounds having medicinal use, the N-acetyl aminophenol must be treated so that it is essentially color-free and retains that state over prolonged periods of storage.
2. Prior Art
N-acetyl aminophenols have customarily been prepared by acetylation of an aminophenol, such as p-aminophenol, with acetic acid or acetic anhydride at atmospheric pressure and temperatures ranging from room temperature to 130.degree. C. There are may variations of this general procedure known to those skilled in the art. An unsatisfactory product is generally obtained due to the readily oxidizable nature of aminophenols and the consequent formation of colored impurities which are carried over to the acetylated product.
Various methods for the decolorization and purification of aminophenols and N-acetyl aminophenols have been suggested.
For example, U.S. Pat. No. 2,013,394 purifies the aminophenol by filtration, alkaline precipitation in the presence of sodium sulfite and solvent extraction. U.S. Pat. No. 2,478,114 treats the aminophenol with reducing agents such as sulfides and sulfites. U.S. Pat. No. 3,917,695 purifies p-aminophenols with acid and aromatic amines or by solvent extraction. U.S. Pat. No. 2,822,370 treats acyl aminophenol with a hot aqueous alkaline steam distillation and subsequent filtration. U.S. Pat. No. 2,945,870 uses a boron condensation catalyst during the initial acetylation reaction and subsequently filters the product with characoal. U.S. Pat. No. 3,042,719 purifies N-acetyl aminophenols by dissolving the N-acetyl aminophenol in water, acidifying the water solution, and filtering with the addition of an alkaline reducing sulfite, e.g., ammonium and alkali metal sulfites, bisulfites and hydrosulfites, U.S. Pat. Nos. 3,081,321 and 3,081,322 acetylated p-aminophenol in the presence of a boron-containing catalyst followed by charcoal filtration. U.S. Pat. No. 3,113,150 filters N-acetyl-p-amino-phenol with carbon black. U.S. Pat. No. 3,748,358 filters N-acetyl-p-aminophenol with the acid treated carbon and a metal chelating agent. U.S. Pat. No. 3,781,354 contacts N-acetyl-p-aminophenol at elevated temperatures with ferric chloride and activated carbon.
Although the various methods described above are all effective to a certain degree in obtaining an N-acetyl aminophenol which is relatively color-free, the decolorized N-acetyl aminophenol may tend to regain its coloration over time due to oxidation. Thus, formulation of an N-acetyl aminophenol into a pharmaceutical product and subsequent warehouse and retail storage of the pharmaceutical product, e.g., analgesic tablets, will result in a product which gradually degrades in color from the original white product.